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Absence of tpr–met and expression of c‐met in human gastric mucosa and carcinoma
Author(s) -
Heideman Daniëlle A. M.,
Snijders Peter J. F.,
Bloemena Elisabeth,
Meijer Chris J. L. M.,
Johan A. Offerhaus G.,
Meuwissen Stefan G. M.,
Gerritsen Winald R.,
Craanen Mikael E.
Publication year - 2001
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.934
Subject(s) - gastric carcinoma , gastric mucosa , carcinoma , medicine , gastroenterology , pathology , cancer , stomach
The c‐met proto‐oncogene, encoding the hepatocyte growth factor receptor, can be activated by various mechanisms. These include, among others, gene amplification with concomitant overexpression and the tpr–met oncogenic rearrangement. In the case of gastric cancer, contradictory results on the presence of the tpr–met oncogenic rearrangement have been published. The current study aimed therefore to assess the prevalence of tpr–met expression in Caucasian gastric adenocarcinomas, to evaluate the importance of this oncogene in their carcinogenesis. In addition, the level of c‐met expression was determined, to evaluate the role of this alternative mode of activation of the proto‐oncogene. A series of Caucasian gastric adenocarcinomas ( n =43) and normal gastric mucosal samples ( n =14) was analysed for tpr–met and c‐met expression. Expression of tpr–met mRNA in the samples was performed by two reverse transcriptase polymerase chain reaction (RT‐PCR) assays, with excellent correlation. The specificity of both methods was confirmed by direct sequencing of the PCR products of the MNNG‐HOS cell line, which is known to contain the rearrangement. The level of c‐met expression was assessed using semi‐quantitative RT‐PCR assays and immunohistochemistry (IHC). None of the normal gastric mucosal or gastric adenocarcinoma samples expressed tpr–met mRNA, as determined by both RT‐PCR assays. Seventy per cent of the adenocarcinomas showed overexpression of c‐met , according to elevated c‐met mRNA levels, compared with the expression level of normal gastric mucosa. A significant correlation was found between the level of c‐met mRNA and protein expression. In conclusion, these results strongly suggest that tpr–met activation does not play a role in Caucasian gastric carcinogenesis, while overexpression of the c‐met gene occurs in the majority of Caucasian gastric adenocarcinomas. Copyright © 2001 John Wiley & Sons, Ltd.